Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea: results from the international sleep apnea global interdisciplinary consortium.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA. METHODS: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy." RESULTS: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders. CONCLUSIONS: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals.

Telemedicine management of obstructive sleep apnea disorder in China: a randomized, controlled, non-inferiority trial.

PURPOSE: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China. METHODS: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed. RESULTS: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs. CONCLUSIONS: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020.

An approach for determining the reliability of manual and digital scoring of sleep stages.

STUDY OBJECTIVES: Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly. METHODS: Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be <5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists. RESULTS: Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%-86.4% among technologists) when using the majority rule, to 96.1 (89.8%-98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing. CONCLUSIONS: Accounting for equivocal epochs provides a more accurate estimate of a scorer's (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.

Cost-effectiveness of a 3-year tele-messaging intervention for positive airway pressure use.

OBJECTIVES: To evaluate the cost-effectiveness of a 3-year tele-messaging intervention for positive airway pressure (PAP) use in obstructive sleep apnea (OSA). STUDY DESIGN: A post hoc cost-effectiveness analysis (from US payers' perspective) of data from a 3-month tele-OSA trial, augmented with 33 months of epidemiologic follow-up. METHODS: Cost-effectiveness was compared among 3 groups of participants with an apnea-hypopnea index of at least 15 events/hour: (1) no messaging (n = 172), (2) messaging for 3 months (n = 124), and (3) messaging for 3 years (n = 46). We report the incremental cost (2020 US$) per incremental hour of PAP use and the fraction probability of acceptability based on a willingness-to-pay threshold of $1825 per year ($5/day). RESULTS: The use of 3 years of messaging had similar mean annual costs ($5825) compared with no messaging ($5889; P = .89) but lower mean cost compared with 3 months of messaging ($7376; P = .02). Those who received messaging for 3 years had the highest mean PAP use (4.11 hours/night), followed by no messaging (3.03 hours/night) and 3 months of messaging (2.84 hours/night) (all P < .05). The incremental cost-effectiveness ratios indicated that 3 years of messaging showed lower costs and greater hours of PAP use compared with both no messaging and 3 months of messaging. Based on a willingness-to-pay threshold of $1825, there is a greater than 97.5% chance (ie, 95% confidence) that 3 years of messaging is acceptable compared with the other 2 interventions. CONCLUSIONS: Long-term tele-messaging is highly likely to be cost-effective compared with both no and short-term messaging, with an acceptable willingness-to-pay threshold. Future long-term cost-effectiveness studies in a randomized controlled trial setting are warranted.

Obesity does not modify the effect of continuous positive airway pressure on insulin resistance in adults with obstructive sleep apnoea.

This study found no evidence that obesity significantly modifies the effect of 4 months of CPAP treatment on HOMA-IR. Longer duration of CPAP treatment may be needed in order to reduce insulin resistance and determine whether obesity modifies the effect. https://bit.ly/3CtX7jZ.

Chronic pain is common and worsens daytime sleepiness, insomnia, and quality of life in veterans with obstructive sleep apnea.

STUDY OBJECTIVES: Chronic noncancer pain (CP) commonly co-occurs with obstructive sleep apnea (OSA) and may contribute to greater symptom burden. The study aims were to (1) characterize CP among veterans with OSA and (2) examine differences in sleepiness (Epworth Sleepiness Scale), insomnia symptoms (Insomnia Severity Index), and quality of life (Short Form Health Survey-20) in veterans with OSA with or without pre-existing CP. METHODS: An observational, cross-sectional, study of 111 veterans with newly diagnosed, untreated OSA was conducted. Descriptive statistics characterized the sample and comorbid CP outcomes. Regression analyses were performed to investigate associations between self-reported CP and sleep-related symptoms or quality of life while controlling for potential confounders. RESULTS: CP was reported by 69.5% (95% confidence interval: 61.8%, 76.2%) of participants. Having CP was associated with increased Epworth Sleepiness Scale (12.7 ± 5.5 vs 10.2 ± 5.2; P = .021) and Insomnia Severity Index scores (18.1 ± 6.2 vs 13.7 ± 7.4; P = .002), and worse quality of life across all Short Form Health Survey-20 domains. CONCLUSIONS: There is a high prevalence of CP among veterans with OSA and symptom burden is higher in patients with OSA and CP. Future investigations should address symptom response and burden to OSA treatment in comorbid OSA and CP to guide outcome expectancies and residual OSA symptom treatment plans. CITATION: Saconi B, Kuna ST, Polomano RC, Compton PA, Keenan BT, Sawyer AM. Chronic pain is common and worsens daytime sleepiness, insomnia, and quality of life in veterans with obstructive sleep apnea. J Clin Sleep Med. 2023;19(6):1121-1132.

Association Between Positive Airway Pressure Adherence and Health Care Costs Among Individuals With OSA.

BACKGROUND: The impact of positive airway pressure (PAP) therapy for OSA on health care costs is uncertain. RESEARCH QUESTION: Are 3-year health care costs associated with PAP adherence in participants from the Tele-OSA clinical trial? STUDY DESIGN AND METHODS: Participants with OSA and prescribed PAP in the Tele-OSA study were stratified into three PAP adherence groups based on usage patterns over 3 years: (1) high (consistently ≥ 4 h/night), (2) moderate (2-3.9 h/night or inconsistently ≥ 4 h/night), and (3) low (< 2 h/night). Using data from 3 months of the Tele-OSA trial and 33 months of posttrial follow up, average health care costs (2020 US dollars) in 6-month intervals were derived from electronic health records and analyzed using multivariable generalized linear models. RESULTS: Of 543 participants, 25% were categorized as having high adherence, 22% were categorized as having moderate adherence, and 52% were categorized as having low adherence to PAP therapy. Average PAP use mean ± SD was 6.5 ± 1.0 h, 3.7 ± 1.2 h, and 0.5 ± 0.5 h for the high, moderate, and low adherence groups, respectively. The high adherence group had the lowest average covariate-adjusted 6-month health care costs ± SE ($3,207 ± $251) compared with the moderate ($3,638 ± $363) and low ($4,040 ± $304) adherence groups. Significant cost differences were observed between the high and low adherence groups ($832; 95% CI, $127 to $1,538); differences between moderate and low adherence were nonsignificant ($401; 95% CI, -$441 to $1,243). INTERPRETATION: In participants with OSA, better PAP adherence was associated with significantly lower health care costs over 3 years. Findings support the importance of strategies to enhance long-term PAP adherence.

The sleep homeostatic response to sleep deprivation in humans is heritable.

STUDY OBJECTIVES: Following sleep deprivation, increases in delta power have historically been used to index increases in sleep pressure. Research in mice has demonstrated that the homeostatic delta power response to sleep deprivation is heritable. Whether this is true in humans is unknown. In the present study, we used delta power and ORP, a novel measure of sleep depth, to investigate the effects of acute sleep deprivation on sleep depth and to assess the heritability of sleep homeostasis in humans. METHODS: ORP and delta power were examined during baseline and recovery sleep following 38 h of sleep deprivation in 57 monozygotic and 38 dizygotic same-sex twin pairs. Two complementary methods were used to estimate the trait heritability of sleep homeostasis. RESULTS: During recovery sleep, ORP was lower and delta power was higher than at baseline, indicating deeper sleep. However, at the end of the recovery night, delta power reached baseline levels but ORP demonstrated incomplete recovery. Both ORP and delta power showed a broad sense heritability of sleep homeostasis following sleep deprivation. The classical approach demonstrated an h2 estimate of 0.43 for ORP and 0.73 for delta power. Mixed-effect multilevel models showed that the proportion of variance attributable to additive genetic transmission was 0.499 (95% CI = 0.316-0.682; p < .0001) for ORP and 0.565 (95% CI = 0.403-0.726; p < .0001 for delta power. CONCLUSIONS: These results demonstrate that the homeostatic response to sleep deprivation is a heritable trait in humans and confirm ORP as a robust measure of sleep depth.

Sleep architecture based on sleep depth and propensity: patterns in different demographics and sleep disorders and association with health outcomes.

STUDY OBJECTIVES: Conventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics. METHODS: We analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP < 0.50) and in full-wakefulness (ORP > 2.25) were each assigned a rank, 1-3, representing first and second digits, respectively, of nine distinct types ("1,1", "1,2" … "3,3"). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined. RESULTS: Three types ("1,1", "1,2", "1,3") were prevalent in OSA and were associated with reduced QOL. Two ("1,3" and "2,3") were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only "1,3" was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types "1,1" and "1,2", and low in "1,3" and "2,3". Prevalence of some types increased with age while in others it decreased. Other types were either rare ("1,1" and "3,3") or high ("2,2") at all ages. CONCLUSIONS: The proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders.

Socioeconomic status impacts blood pressure response to positive airway pressure treatment.

STUDY OBJECTIVES: Positive airway pressure (PAP) treatment of obstructive sleep apnea reduces blood pressure (BP). Retrospective data suggest that African Americans (AA), a group at high-risk for hypertensive organ dysfunction, may have a greater BP response to PAP therapy than European Americans (EA). We examined the difference in 24-hour BP response to 3 months of PAP treatment between AA and EA. METHODS: Participants (n = 259, 161 AA and 98 EA) with apnea-hypopnea index ≥ 15 events/h from 2 prospective cohorts were included. t-Tests and multiple linear regression were used to examine BP outcomes in AA vs EA, adjusting for PAP adherence, socioeconomic status, and baseline characteristics. RESULTS: Participants were middle aged (mean ± SD, 53.8 ± 9.3 years), 86% (227) men, apnea-hypopnea index 35.6 ± 19.2 events/h, and PAP adherence of 3.36 ± 2.24 h/day. The reductions in 24-hour systolic and diastolic BP (mm Hg) were not different in AA vs EA (systolic = -1.13 ± 12.1 vs -0.61 ± 12.8, P = .80 and diastolic = -0.74 ± 7.9 vs -0.80 ± 7.4, P = .96), and race was not a predictor of 24-hour systolic or diastolic BP reduction (P = .75 and 0.54). Socioeconomic status and PAP adherence demonstrated a significant interaction; low socioeconomic status was associated with an increase in 24-hour systolic BP (ß = 19.3, P = .03) in the absence of PAP use but a greater reduction in 24-hour systolic BP with higher PAP adherence (ß = -3.96, P = .03). CONCLUSIONS: Twenty-four hour BP response to PAP treatment is similar in AA and EA. Adherence to PAP treatment is more effective in improving 24-hour systolic BP in those with low SES. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Race and CPAP Effectiveness (RACE); URL: https://clinicaltrials.gov/ct2/show/NCT01960465; Identifier: NCT01960465 and Registry: ClinicalTrials.gov; Name: The Effects of Treating Obese and Lean Patients with Sleep Apnea (PISA); URL: https://clinicaltrials.gov/ct2/show/NCT01578031; Identifier: NCT01578031. CITATION: Imayama I, Gupta A, Yen PS, et al. Socioeconomic status impacts blood pressure response to positive airway pressure treatment. J Clin Sleep Med. 2022;18(5):1287-1295.

Different components of excessive daytime sleepiness and the change with positive airway pressure treatment in patients with obstructive sleep apnea: Results from the Icelandic Sleep Apnea Cohort (ISAC).

Excessive daytime sleepiness includes both an inability to stay awake during the day and a general feeling of sleepiness. We describe different dimensions of daytime sleepiness in adults with moderate-severe obstructive sleep apnea (OSA) before and after 2 years of positive airway pressure (PAP) treatment. Using the Epworth Sleepiness Scale (score >10 defined as "risk of dozing") and Basic Nordic Sleep Questionnaire (feeling sleepy ≥3 times/week defined as "feeling sleepy"), participants were categorised into sleepiness phenotypes labelled non-sleepy, risk of dozing only, feeling sleepy only, or both symptoms. Participants repeated baseline assessments and PAP adherence was evaluated after 2 years. PAP-adherent subjects with sleepiness symptoms at both baseline and follow-up were considered persistently sleepy. Of the 810 participants, 722 (89%) returned for follow-up. At baseline, 17.7% were non-sleepy, 7.7% were at risk of dozing only, 24.7% were feeling sleepy only, and 49.9% had both symptoms. PAP adherence did not differ by baseline sleepiness phenotype. Patients with risk of dozing demonstrated greater PAP benefits for sleepiness symptoms than non-sleepy and feeling sleepy only phenotypes. Using these phenotypes, 42.3% of PAP users had persistent sleepiness; they had less severe OSA (p < 0.001), more persistent OSA symptoms and more often had symptoms of insomnia than patients in whom sleepiness resolved. Our present results, therefore, suggest that measuring the risk of dozing and the feeling of sleepiness reflect different sleepiness components and may respond differently to PAP. Patients feeling sleepy without risk of dozing may need more thorough evaluation for factors contributing to sleepiness before initiating treatment.

Racial Differences in Functional and Sleep Outcomes with Positive Airway Pressure Treatment.

It is unclear if the response to positive airway pressure (PAP) treatment is different between African American (AA) and European Americans (EA). We examined whether race modifies the effects of PAP on sleep and daytime function. We assessed Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire, Psychomotor Vigilance Task and actigraphy in 185 participants with moderate-to-severe obstructive sleep apnea before and 3-4 months after PAP treatment. The participants were middle-aged (mean, 55.1 years), 83.8% men and 60.5% AA. Linear regression models were used to examine the effect of race on outcomes. The AA had smaller reductions in ESS (mean change (95% confidence interval, CI) AA, -2.30 [-3.35, -1.25] vs. EA, -4.16 [-5.48, -2.84] and frequency of awakenings (AA, -0.73 [-4.92, 3.47] vs. EA, -9.35 [-15.20, -3.51]). A race × PAP usage interaction term was added to the model to examine if the change in outcomes per 1 h increase in PAP usage differed by race. AA exhibited greater improvement in wake after sleep onset (ß (95% CI) AA, -8.89 [-16.40, -1.37] vs. EA, 2.49 [-4.15, 9.12]) and frequency of awakening (ß (95% CI) AA, -2.59 [-4.44, -0.75] vs. EA, 1.71 [-1.08, 4.50]). The results indicate the importance of race in evaluating outcomes following PAP treatment.

Randomized Noninferiority Trial of Telehealth Delivery of Cognitive Behavioral Treatment of Insomnia Compared to In-Person Care.

Objective: Insomnia is prevalent and is associated with a range of negative sequelae. Cognitive behavioral treatment for insomnia (CBT-I) is the recommended intervention, but availability is limited. Telehealth provides increased access, but its efficacy is not certain. The objective of this study was to compare the efficacy of CBT-I delivered by telehealth to in-person treatment and to a waitlist control.Methods: Individuals with DSM-5 insomnia disorder (n = 60) were randomized to telehealth CBT-I, in-person CBT-I, or 8-week waitlist control. CBT-I was delivered over 6-8 weekly sessions by video telehealth or in-person in an outpatient clinic. Follow-up assessments were at 2 weeks and 3 months posttreatment. The Insomnia Severity Index (ISI) was the primary outcome. Change in ISI score was compared between the CBT-I group in an intent-to-treat, noninferiority analysis using an a priori margin of -3.0 points. All analyses were conducted using mixed-effects models. Data collection occurred from November 2017-July 2020.Results: The mean (SD) change in ISI score from baseline to 3-month follow-up was -7.8 (6.1) points for in-person CBT-I, -7.5 (6.9) points for telehealth, and -1.6 (2.1) for waitlist, and the difference between the CBT-I groups was not statistically significant (t28 = -0.98, P = .33). The lower confidence limit of this between-group difference in the mean ISI changes was greater than the a priori margin of -3.0 points, indicating that telehealth treatment was not inferior to in-person treatment. There were significant improvements on most secondary outcome measures but no group differences.Conclusions: Telehealth CBT-I may produce clinically significant improvements in insomnia severity that are noninferior to in-person treatment. CBT-I is also associated with significant gains across a range of domains of functioning. Telehealth is a promising option for increasing access to treatment without loss of clinical gains.Trial Registration: ClinicalTrials.gov identifier: NCT03328585.

Sleep disordered breathing as a cause and consequence of stroke: A review of pathophysiological and clinical relationships.

Stroke is the leading cause of death and disability globally. Sleep disordered breathing (SDB), a potentially modifiable risk factor of stroke, is highly prevalent in stroke survivors. Evidence supports a causal, bidirectional relationship between SDB and stroke. SDB may increase the risk of stroke occurrence and recurrence, and worsen stroke outcome. While SDB is associated with an increased incidence of hypertension and cardiac arrhythmias, both of which are traditional stroke risk factors, SDB is also an independent risk factor for stroke. A number of characteristics of SDB may increase stroke risk, including intermittent hypoxemia, sympathetic activation, changes in cerebral autoregulation, oxidative stress, systemic inflammation, hypercoagulability, and endothelial dysfunction. On the other hand, stroke may also cause new SDB or aggravate preexisting SDB. Continuous positive airway pressure treatment of SDB may have a beneficial role in reducing stroke risk and improving neurological outcome after stroke. The treatment should be considered as early as possible, particularly when SDB is present post-stroke. The goal of this review is to highlight the strong link between SDB and stroke and to raise awareness for practitioners to consider the possibility of SDB being present in all stroke survivors.

Home sleep apnea testing of adults with chronic heart failure.

STUDY OBJECTIVES: To evaluate home sleep apnea testing (HSAT) using a type 3 portable monitor to help diagnose sleep-disordered breathing (SDB) and identify respiratory events including obstructive sleep apnea, central sleep apnea, and Cheyne-Stokes respiration in adults with stable chronic heart failure. METHODS: Eighty-four adults with chronic heart failure (86.9% males, age [mean ± standard deviation] 58.7 ± 16.3 years, body mass index 29.4 ± 13.0 kg/m², left ventricular ejection fraction 40.3% ± 11.5%) performed unattended HSAT followed by an in-laboratory polysomnography (PSG) with simultaneous portable monitor recording. RESULTS: The apnea-hypopnea index was 22.0 ± 17.0 events/h according to HSAT, 26.8 ± 20.5 events/h on an in-laboratory portable monitor, and 23.8 ± 21.3 events/h using PSG (P = .373). A Bland-Altman analysis of the apnea-hypopnea index using HSAT vs PSG showed a mean difference (95% confidence interval) of -2.4 (-4.9 to 0.1) events/h and limits of agreement (±2 standard deviations) of -24.1 to 19.2 events/h. HSAT underestimated the apnea-hypopnea index to a greater extent at a higher apnea-hypopnea index (rho = -.358; P < .001). Similar levels of agreement from HSAT vs PSG were observed when comparing the obstructive apnea index, central apnea index, and percentage of time in a Cheyne-Stokes respiration pattern. When we used an apnea-hypopnea index ≥ 5 events/h to diagnose SDB, HSAT had 86.7% sensitivity, 76.5% specificity, 92.9% positive predictive value, and 61.9% negative predictive value compared to PSG. Detection of Cheyne-Stokes respiration using HSAT showed 94.6% sensitivity, 91.1% specificity, 88.6% positive predictive value, and 97.6% negative predictive value compared to PSG. CONCLUSIONS: HSAT with a type 3 portable monitor can help diagnose SDB and identify obstructive sleep apnea, central sleep apnea, and Cheyne-Stokes respiration events in adults with chronic heart failure.

Where to Next for Optimizing Adherence in Large-Scale Trials of Continuous Positive Airway Pressure?

Large-scale randomized trials of positive airway pressure (PAP) efficacy have been largely negative but PAP adherence was notably suboptimal across the trials. To address this limitation, evidence-based PAP adherence protocols embedded within the larger trial protocol are recommended. The complexity of such protocols depends on adequacy of resources, including funding and inclusion of behavioral scientist experts on the scientific team, and trial-specific considerations (eg, target population) and methods. Recommendations for optimizing PAP adherence in large-scale trials are set forth that address rigor and reproducibility.

Effect of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Cardiac Remodeling as Assessed by Cardiac Biomarker and Magnetic Resonance Imaging in Nonobese and Obese Adults.

It is unknown whether obesity modifies the effect of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy on cardiac remodeling and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. We compared NT-proBNP and cardiac magnetic resonance imaging in adults without OSA (n=56) and nonobese (n=73; body mass index <30 kg/m2) and obese (n=136; body mass index ≥30 kg/m2) adults with OSA. We also investigated these traits in nonobese (n=45) and obese (n=78) participants with OSA adherent to 4 months of PAP treatment. At baseline, left ventricular mass to end-diastolic volume ratio, a measure of left ventricular concentricity, was greater in both nonobese and obese participants with OSA compared with those without OSA. Participants with OSA and obesity exhibited reduced phasic right atrial function. No significant differences in baseline NT-proBNP were observed across groups. The effect of PAP treatment on NT-proBNP and left atrial volume index was significantly modified by obesity. In nonobese participants, PAP therapy was associated with a decrease in NT-proBNP (P<0.0001) without a change in left atrial volume index, whereas in obese participants, PAP was associated with an increase in left atrial volume index (P=0.006) without a change in NT-proBNP. OSA was associated with left ventricular concentric remodeling independent of obesity and right atrial dysfunction in participants who were obese. PAP treatment was associated with reduced NT-proBNP in nonobese participants with OSA, but left atrial enlargement in obese participants with OSA, suggesting that PAP-induced reduction in BNP release (which is known to occur during obstructive apnea episodes) may lead to volume retention in obese participants with OSA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01578031.

Changes in sleepiness and 24-h blood pressure following 4 months of CPAP treatment are not mediated by ICAM-1.

OBJECTIVE: Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment. METHODS: The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use. RESULTS: Among 140 adults (83% men), mean (± SD) body mass index (BMI) was 31.5 ± 4.2 kg/m2, and apnea-hyopnea index (AHI) was 36.8 ± 15.3 events/h. Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures. CONCLUSION: Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or not other biomarkers may have a role in mediating these treatment outcomes in adults with OSA.